Production of n, n-dialkylamino alcohols



Patented Dec. 26, 1944 PRODUCTION OF N,N-DIALKYLAMINO ALCOHOLS Lucas P. Kyrides, Webster Groves, Mo., assignor to Monsanto Chemical Company, St. Louis, Mo., a corporation of Delaware No Drawing. Application October 29, 1942, Serial No. 463,809

Claims. (Cl. 260-584) The present invention relates to the production of N,N-dialkylamino alcohols,- particularly N,N- diethyl-l-amino-4-pentanol, by the reaction of secondary, amines with polyhydric alcohols.

The principal object of the presentinvention is to provide an improved method for the production of N,N-dialkylamino alcohols, such as N,N-diethyl1-amino-4-pentanol. Another object of the invention is to provide a method of producing N,N-diethyl-1-amino-4-pentanol in high yields from readily available chemical substances. Further objects and advantages of the invention, some of which are referred to specifically hereinafter, will be apparent to those skilled in the art.

Heretofore no general method has been available for the preparation of N,N-dialkylamino alcohols directly from polyhydric alcohols. It has been known that ethylene oxide and alkyl-substituted ethylene oxides could be reacted with secondary amines (dialkyl amines) to yield a dialkylaminoalkanol. For example, Knorr and Matthes, Berichte, 1901, vol. 34, page 3482, reacted ethylene oxide with dimethylamine to obtain 2-dimethylaminoethanol (1-hydroxy-2-dimethylaminoethane), according to the following equation:

The method has been further extended to substituted ethylene oxides (see German Patent 'No. 199,148; Frdl. IX, 975). This method, however, is capable of yielding only dialkylamino alcohols in which the dialkylamino group and the hydroxyl group are on adjacent carbon'atoms. It, furthermore, is not the equivalent of the reaction of polyhydric alcohols with secondary amines, since polyhydric alcohols are not substantially reactive under conditions which are favorable for the reaction of ethylene oxides.

Another general method of preparing dialkylamino alcohols which has been applied generally consists in reacting a halogenated alcohol with a secondary amine, in which reaction the halogen is substituted by the dialkylamino radical of the secondary amine, according to the following general reaction:

This reaction is also limited in its application since halogenated alcohols embodying the halogen and hydroxyl radicals on the desired carbon atoms are not readily prepared. In preparing halogenated alcohols, all possible isomers are generally formed, hence the yield of any particular isomer is generally but a small fraction of the total yield.

A dialkylamino alcohol such as N,N-diethyl-lamino-4-pentanol, which may be represented as:

' H c2115 CH -CH-OHzOHzCHz-N cannot be prepared by the first of the foregoing methods, namely, the reaction of a secondary amine with an ethylene oxide; when prepared .from the corresponding halogenated alcohol, the

yield is low, based on the raw material used for the preparation of the halogenated alcohol. The compound has usually been prepared by indirect methods (see, for example, Schulemann et al., Patent No. 1,747,531)

N,N=diethyl-1-amino-4-pentanol can readily be converted by reaction with ammonia to 5-diethylamino-2-aminopentane (4-diethylamino-1- methylbutylamine, N',N'-diethyl-1, 4-pentanediamine,

10-(4-diethylamino-l-methyl-butylamino)- acridine (see Mietzsch and Mauss, Patent No. 2,113,- 357; also Knunyantz et al., Bull. acad. sci.

. U. R. S. S., Classe sci. math. nat., 1934, pages 165- I 176; Chem. Abs., 1934, vol. 28, page 4837 and Drozdov, J. Gen. Chem. (U. S. S. R.), 1938, vol. 8,

' pages 937-42 and 1192-3; Chem. Abs., 1938, vol.

33, pages 1330 and 4251).

I have found that N,N-diethyl-l-aminolpentanol can be prepared in good yields from 1,4- pentanediol by heating a reaction mixture of 1,4- pentanediol and diethylamine in the presence of a metal hydrogenation catalyst at temperatures within the range of approximately to C. The reaction proceeds apparently as follows:

N,N-diethyl-l-amino 4-pentanol It was unexpected that the reaction would proceed without substantial substitution of the hydroxyl group in the 4 position of 1,4-pentanediol.

Whether this preferential amination of the primary carbinolradical; of the diol is due to steric hindrance or to other factors, I am unable to state. The reaction is general, as I have found-,, polyhydric alcohols which contain both a primary and secondary carbinol radical react with di.-.,

alkylamines (secondary amines) to effect a substitution by the dialkylamino, radical of one hydroxyl radical of the; primary carbinol (CH2OH) radical, in preference to a hydroxyl: I

radical of a secondary carbinol (CHOI-I-) rad;- ical of the alcohol.

1,4-pentanediol is a readily obtainable substance and by means of my process is readily- VI, Residu,e.The fractionremained after the foregoing fractions were collected.

The yields of the various fractions obtained in this example were as follows:

erg in origins Fraction grams pegltalne The-values in the, column percent original pentanediol correspond to the percentage which the particular: fraction. represents; in terms of pentanediol. originally; charged. In. this. calculation only fractions III to VI, inclusive. were con-- sidered, all of; which v exceptfraction IV (which was N,N-.,-diethyl-l-aminoal pentanol) were. considered; to, be pentanediol. or. equivalent weight.

Preferred methods of practicing the process ofv my invention are illustrated in the examples which follow:

EXAMPLE 1 A steel autoclave provided with av stirrer was charged with 300 grams of 1,4-pentanediol, 250 grams (350 ml.) of diethy-lam-ine and 20 grams of a nickel catalyst-prepared by the thermal decomposition of nickel formate inmineral: oil. The;-

catalystwas washed with-..ethyl'alcoholz before addition-to the charge in-- the autoclave. The

charge was then heated with-stirring under; pres-..

sure .for a Deriod'ofi4 hoursat a.temperature. varying within the-rangelof 160 to 180?*-C: The, charge was thencooled, the catalysttwassepa-v rated by filtration andthe;cata-lyst-freereacti'on mixture was subjected to distillation; Thefollowing distillation fractions wereicollected .in the order indicated."

I. Recoveredamz'nes and.watex=.-?This fractionincluded all material which distilled up tea teme perature of approximately 160 C; The; major portion of the amines distilled; between 5.4". and 74 C.

II, Trapped fraction-#This fraction was. that which came over after fractionrI and upto a. distilling temperature of approximately 100. C: at a pressureof to mm. of mercury. It was collected in a cooled trap.

III. Forerunm'ngs. This material distilled after fraction II had been separated andcon sisted of thatportion which had a boiling point up to 118 C. at a pressure of 35 mm. of mercury.

IV. N,N-diethyl-1-ammo-4-1 entanol. This was the desired product and was collected within the distillingrange of 118-to 120.-" at-a pressure of 35 mm. of mercury.

V. Recovered 1,4-pentanedzoZ.-'This fraction was collected between the distilling range of 120 to 140 C. at 35 mm.,, thepressure. at the endof this fraction being reduced to about .8. to .10 mm.. to distill over any;of;the material remainingyin the column.

for weight of original. pentanediol. The weight.

of fraction, IV was converted. to Weight of pena sum g, the fracti n t e. pur .NN- diethyl:l amino l pentanol, by using the stoichiometrical, factor 0.654; this calculatedlweight of pentanedi'olwasused, for obtaining the corr,e,

p n in pe e ri inal. n anediotf" Which.

alsorepresentspercentage 0f the. theoretical yield of N,N-diethyl-l-amino-4-pentanediol' based on the amount of lA-pentanediol used; The per cent pentanediol recovery-represents the total percentages of pentanediol accounted-for inthis;

manner EXAMPLE: 2-

E amp e 1. was n ted: y; us na, h w v r; an: other batch of a similar, nickel catalyst which not Wa hed. h: et nol; mlr nsteadmf. 35 0. ml. of diethyl-amine andheating' at: ?C

om what ower:- han-,. n; xamp1e; .;and;mori e: ighe oi n ma eri ls rez ormed-i .asl sindir cated. the following results which are 1'85, pertedtas n. x mn c;

EXAMPLE 3 Example 1 was repeated with the following han s; 4 ift en 1l5)-s, m a.. nsteadaof *werammmm he atch: f: t mores cti e. nickel; ata yst prepared; by the the mal. de omposition. of

nickeltformatezinzwhich oil wast-used; Temperature; ofbheating' wasdSOfiG: Period of heating was 10 hours.

' tion reactions.

Th -results, reported as in' Example 1, were as follows:

' Weightin F9 Fraction original grams ,pentanodiol I 154 IL.-- i 37 III--- I 10 ,3 IV. 133 '29 V 132 44 VI--- l Per cent pentanediol recovery. 91

Aminatzon of N,N-diethyI-l-amino-4-pentanol weights and characteristics are approximately as follows:

Distillation Fraction range Weight Grams I 5-diethylamino-2-aminopentane. 97l02/34 mm. 119 II Recovered N,N-diethyl-l-aml02117/34mn1. 153

ino-4 pentanol.

Although the foregoing examples relate specifically to the reaction of 1,4-pentanediol with diethylamine, the process is applicable generally to the reaction of polyhydric alcohols which embody at least one primary carbinol and at least one secondary carbinol radical with secondary aliphatic amines. Typical examples of such polyhydric alcohols which may be used in the process of this invention are propylene glycol (1,2-propanediol) 1,2-butanediol, 1,3-butanediol, 1,3-pentanediol, 1,4-pentanediol, etc. All of the foregoing specifically named polyhydric alcohols are hydroxy-l-alkanols containing at least one terminal primary carbinol radical and at least on secondary carbinol radical. Aliphatic secondary amines which may be used in the process are dimethylamine, diethylamine, di-n-propylamine, diisopropylamine, dibutylamines and the like. The reaction involved in the process comprises a substitution of a hydroxyl of a primary carbinol radical in preference to a hydroxyl of a secondary carbinol radical of the polyhydric alcohol.

Nickel hydrogenation catalysts are the preferred catalysts, although other metal hydrogenation catalysts such as platinum, palladium, cobalt, copper and similar catalysts may be used.

.The catalyst may be deposited upon a carrier,

if desired, as is well understood in the art. Although the reaction does not involve a hydrogenation as such, yet .it is facilitated by catalysts which are known 'to promote hydrogena- Some of the foregoing specified catalysts are more reactive than others and temperatures and other conditions of reaction are preferably adjusted to compensate for these differences in activity.

The reaction normally proceeds at temperatures within the range of approximately 120 C. to approximately 180 C. In order to shorten th reaction period, higher temperatures (for example, up to about1250 C.) may-be used. The optimum conditions of reaction, that is, the optimum temperature and period of reaction-will vary somewhat with the various polyhydric alcohols and secondary amines, their. relative proportions and the amounts which are being subjected to reaction." The results reported in the examples are not to be understood to, represent the best yields of which the method is capable,

however. H 1 3 V Inasmuch as the I foregoing description .comprises preferred embodiments of the invention, it istobeunderstood that the invention is not limited thereto and. that changes and modifications may be made therein without xdeparting substantially from the invention, which is defined in the appended claims.

I claim:

l. The process of producing an N,N-dialkyl amino alcohol from an aliphatic polyhydric alcohol having at least one primary carbinol radical and at least one secondary carbinol radical, which comprises reacting said polyhydric alcohol with a secondary aliphatic amine, in the presence of a metal hydrogenation catalyst at a tem perature above approximately 0., whereby a hydroxyl radical of a primary carbinol radical of the polyhydric alcohol is substituted by the dialkylamino radical in preference to the hydroxyl radical of a secondary carbinol radical.

2. The process of producing an N,N-dialkylamino alcohol from an aliphatic polyhydric alcohol having at least one primary carbinol radical and at least one secondary carbinol radical, which comprises reacting said polyhydric alcohol with a secondary aliphatic amine, in the presence of. a metal hydrogenation catalyst at a temperature within the range of approximately 120 to 250 0., whereby a hydroxyl radical of a primary carbinol radical of' the polyhydric alcohol is substituted by the dialkylamino radical in preference to the hydroxyl radical of a secondary carbinol radical.

3. The process of producing an N,N-dialkylamino alcohol from an aliphatic polyhydric alcohol having .at least one primary carbinol radical and at least one secondary carbinol radical, which-comprises reacting said polyhydric alcohol with a secondary aliphatic amine, in the presence of a metal hydrogenation catalyst at a temperature within the range of approximately 120 to 180 C., whereby a hydroxyl radical of a primary carbinol radical of the polyhydric alcohol is substituted by the dialkylamino radical in preference to the hydroxyl radical of a secondary carbinol radical.

4. The process for the production of N,N-diethy1-1-amino-4-pentano1 which comprises reacting l/l-pentanediol with diethylamine in the presence of a metal hydrogenation catalyst at a temperature above approximately 120 C.

5. The process for the production of N,N-diethyl-l-aminol-pentanol which comprises reacting 1,4-pentanedio1 with diethylamine in the presence of a metal hydrogenation catalyst at a range of approximately Illa-inletmacaw?off-pnoduclngianmmNrdialkylamino alcohol from an aliphatic polyhydrio; a1 coholhavingatleastoneeprimary.carbinolradical and-,at'Jeastv-oneh secondary carbinol radical which comprises-reacting in the liquid pha'se said polyh'ydrio'albohol with a. secondary aliphatic amine q'ialkylamino radi al:

in the presence of a metal hydrogenation catalyst at a temperature above 120 Ci, whereby a hy droxyl radical ofwpzfimary-carbinolradical? of the pOISIhydric: alkiohoYis substituted by the? LUCKSPTKYRIDES; 

